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EC number: 203-398-6 | CAS number: 106-44-5
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
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Carcinogenicity
Administrative data
Description of key information
There is no carcinogenicity bioassay or other chronic study available to assess the carcinogenic potential of p-cresol.
However, the recently published studies on carcinogenicity with m/p-cresol mixture (60:40; US Department of Health and Human services 2007) is considered.
Key value for chemical safety assessment
Carcinogenicity: via oral route
Link to relevant study records
- Endpoint:
- carcinogenicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: only male rats in test
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 451 (Carcinogenicity Studies)
- Principles of method if other than guideline:
- Groups of 50 male rats were fed diets containing 0, 1,500, 5,000 or 15,000 ppm m-/p-cresol (equivalent to average daily doses of approximately 70, 230, or 720 mg cresols/kg body weight) for 105 weeks.
All animals were observed twice daily. Body weights were recorded at the beginning of the study, weekly for the first 13 weeks, at 4-week intervals thereafter, and at study termination. Clinical findings
were recorded during week 5 of the study, at 4-week intervals thereafter, and at study termination.
Complete necropsies and microscopic examinations were performed on all rats. At necropsy, all organs and tissues were examined for grossly visible lesions, and all major tissues were fixed and preserved in 10% neutral buffered formalin (eyes were first placed in Davidson’s solution), processed and trimmed, embedded in paraffin, sectioned to a thickness of 4 to 6 μm, and stained with hematoxylin and eosin for microscopic examination. For all paired organs (e.g., adrenal gland, kidney, ovary), samples from each organ were examined. For extended evaluation of renal proliferation lesions, additional sections of both kidneys from the residual formalin-fixed wet tissues were obtained for each male rat, imbedded in separate paraffin blocks, and step sectioned at 1 mm intervals. Three (left kidney) or four (right kidney) sections were examined for each rat. - GLP compliance:
- yes
- Species:
- rat
- Strain:
- other: Fisher 344/N
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Taconic Laboratory Animals and Sevices, Germantown, NY
- Age at study initiation: 6 weeks
- Housing: 2-3 rats/cage
- Diet: ad libitum
- Water: ad libitum):
- Acclimation period: 11 days
ENVIRONMENTAL CONDITIONS
- Temperature (°F): 72
- Humidity (%): 50
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12
- Route of administration:
- oral: feed
- Vehicle:
- unchanged (no vehicle)
- Details on exposure:
-
DIET PREPARATION
- Rate of preparation of diet (frequency): monthly
- Mixing appropriate amounts with NTP-2000 food
- Storage temperature of food: at 25 °C in the dark
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Periodic analyses of the dose formulations were conducted by the study laboratory usinng GC. The dose formulations were analyzed
approximately every 3 months.All of the dose formulations analyzed for rats were within 10 % of the target concentration. - Duration of treatment / exposure:
- 105 weeks
- Frequency of treatment:
- daily
- Post exposure period:
- no
- Remarks:
- Doses / Concentrations:
0, 1500, 5000 or 15000 ppm = equivalent to average daily doses of approx. 0, 720, 230, or 720 mg/kg bw/day
Basis:
nominal in diet - No. of animals per sex per dose:
- 50 male rats per dose
- Control animals:
- yes, plain diet
- Details on study design:
- - Dose selection rationale: the highest exposure concentrations was based on the minimal toxicity observed at this level
in the 13 week study with m/p-cresol mixture - Positive control:
- no
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice daily
DETAILED CLINICAL OBSERVATIONS: yes
- Time schedule:
Clinical findings were recorded during week 5 of the study, at 4 week intervallsthereafter and at terminiation
BODY WEIGHT: Yes
- Time schedule for examinations:
at the beginning of the study weekly for the first 13 weeks, at 4 week intervals thereafter and at study termination
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined Yes
at the beginning of the study weekly for the first 13 weeks, at 4 week intervals thereafter:
Food consumption calculated as mean g/day
Compound consumption calculated as mean mg/kg bw/day
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: No
CLINICAL CHEMISTRY: No
URINALYSIS: No
NEUROBEHAVIOURAL EXAMINATION: No
- Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
was performed on all rats
HISTOPATHOLOGY: Yes
complete histopathology was performed on all rats. In addition to gross sessions and tissue masses, the following tissues were examined:
adrenal gland, none with marrow, brain, esophagus, eye, hardrian gland, heart and aorta, large
intestine, small intestin kidney, liver, lung, mainstem bronchi, lymph nodes (mandibular and mesenteric), mammary gland, nose, pancreas, parathyroid gland, pituitary gland, preputial gland, prostate gland, salivary gland, skin, spleen, stomach (forestomach and glandular), testis with epididymis and seminal vesicle, thymus, thyroid gland, trachea and urinary bladder.
For all paired organs samples from each organ were examined.
For extended evaulation of renal proliferation lesions, additional sections of both kidneys from the residual formalin-fixed wet tissues were obtained for each male rat. 3 sections of the left kidney and 4 sections of the right kidney were examined for each rat. - Other examinations:
- no
- Statistics:
- Kaplan Meier, Cox-method, Tarone's life-table test, Poly-k-test,
- Clinical signs:
- effects observed, treatment-related
- Mortality:
- mortality observed, treatment-related
- Body weight and weight changes:
- effects observed, treatment-related
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- no effects observed
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- effects observed, treatment-related
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Histopathological findings: neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- at 15000 ppm in 4/50 rats renal tubular adenomas ; increase not significant but exceeding historical controls of the laboratory [1/297 [feed studies])
- Details on results:
- see section "remarks on results"
mean body weights of the 15000 ppm group were less than those of the controls throughout the study and decreased to 15 % less than that of the controls by the end of the study
There were no clinical findings related to exposure to cresols.
Equivocal finding :
The incidence of renal tubule adenomas was increased in the 15000 ppm group and the incidence exceeded the historical range for controls in feed studies (0-2 %). - Dose descriptor:
- LOAEL
- Effect level:
- 720 mg/kg diet
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- other: Under the conditions of these 2-year studies, there was equivocal evidence of carcinogenic activity of 60:40 m-/p-cresol in male F344/N rats based on the marginally increased incidence of renal tubule adenoma.
- Remarks on result:
- other: Effect type: carcinogenicity
- Dose descriptor:
- NOAEL
- Effect level:
- 230 mg/kg diet
- Based on:
- test mat.
- Sex:
- male/female
- Remarks on result:
- other: Effect type: carcinogenicity
- Executive summary:
Under the conditions of these 2-year studies (oral feed, 0, 1500, 5000 or 15000 ppm = equivalent to average daily doses of approx. 0, 720, 230, or 720 mg/kg bw/day), there was equivocal evidence of carcinogenetic activity of 60:40 m/p-cresol in male F344/N rats based on the marginally increased incidence of renal tubule adenoma. The LOAEL(male rats) is therefore 720 mg/kg bw/day.
Reference
Concentration in feed
0, 1,500, 10,000 or 15,000 ppm
equivalent to average daily doses of approximately 0, 70, 230, 720 mg/kg bw/day
Body weights
15,000 ppm group: less than the control group
Survival rates : 33/50, 34/50, 33/50, 31/50
Nonneoplastic effects
----Kidney
pelvis, transitional epithelium, hyperplasia (0/50, 0/50, 2/50, 8/50);
severity of nephropathy (1.4, 1.4, 1.7, 2.1)
----Nose:
goblet cell, hyperplasia (23/50, 40/50, 42/50, 47/50);
respiratory epithelium, hyperplasia (3/50, 17/50, 31/50, 47/50)
respiratory epithelium, metaplasia, squamous (0/50, 1/50, 8/50, 40/50);
inflammation (17/50, 19/50, 19/50, 28/50)
----Liver:
eosinophilic focus (14/50, 14/50, 13/50, 23/50)
Neoplastic effects
-----None
Equivocal findings:
---- Kidney:
renal tubule adenoma
--standard evaluation - 0/50, 0/50, 0/50, 3/50;
--standard and extended evaluations combined - 0/50, 0/50, 0/50, 4/50(8%)
Level of evidence of carcinogenic activity : equivocal evidence
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- NOAEL
- 230 mg/kg bw/day
- Study duration:
- chronic
- Species:
- rat
- Quality of whole database:
- The materials/methods and results are described in detail und are sufficient for evaluation.
Carcinogenicity: via inhalation route
Endpoint conclusion
- Endpoint conclusion:
- no study available
Carcinogenicity: via dermal route
Endpoint conclusion
- Endpoint conclusion:
- no study available
Justification for classification or non-classification
No classification is required
Additional information
There is no carcinogenicity bioassay or other chronic study available to assess the carcinogenic potential of p-cresol.
However, for read across purposes, the recently published studies on carcinogenicity with m/p-cresol mixture (60:40; US Department of Health and Human services 2007) is considered.
In 2007, US Health and Human Services published a Toxicity and Carcinogenicity Study in which only male rats or only female mice were fed m/p-cresol mixture over a period of two years without interim kill. Neither absolute/relative organ weights nor blood biochemistry data were reported so far. The report contains only histopathological data.
Rat study
Male F344/N rats received in feed 0, 1500, 5000, or 15000 ppm (= equivalent to daily doses of approx. 0, 70, 230 or 720 mg/kg bw/day) for 105 weeks. Under the condition of these 2-year studies, there was equivocal evidence of carcinogenic activity on m/p-cresol based on the 4/50 male rats with renal tubular adenomas. The incidence of these neoplasms was not significant but exceeded the historical control data of the laboratory (1/297 [feed studies]).
Mouse study
Female B6C3F1 mice received in feed 0, 1000, 3000, 10000 ppm (= equivalent to dailydoses of approx. 0, 100, 300 or 1040 mg(kg bw/day) for 104-105 weeks. Under the conditions of these 2-year studies there was some evidence of carcinogenic activity of m/p-cresol mixture based on the increased incidence of forestomach squamous cell papillomas. However, there is no human counterpart for the rodent forestomach (Proctor et al., Toxicol Sci 98, 313 -326, 2007). Therefore, the forestomach squamous cell paplillomas are of minor significance for the human situation. In addition, due to the corrosive property of the test substance, chronic irritation is expected to be the mode of action.
Justification for selection of carcinogenicity via oral route endpoint:
A NTP technical report on the toxicology and carcinogenesis studies of cresols (CAS no. 1319-77-3) in male F344/N rats and female B6C3F1 mice (feed studies). The most reliable study concernig effects relevant for humans is used as key value and for classification.
Carcinogenicity: via oral route (target organ): urogenital: kidneys
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